Light absorbed by visual pigments of rod and cone photoreceptor cells converts 11-cis-retinal to all-trans-retinal, triggers the phototransduction cascade and ultimately modifies the rate of neurotransmitter release. A series of enzymatic reactions produces 11-cis-retinal from all-trans-precursor(s) in adjacent RPE cells. Diffusion of retinoids between RPE and photoreceptor cells completes this visual or regeneration cycle. The overall process involves the concerted action of enzymes, retinoid-binding proteins, and discrete membranous compartments. The long-range goal of my research project is to provide new molecular information about the regeneration of visual pigments in mammalian rods and cones. The proposed work is based on preliminary results and will feature cellular retinaldehyde-binding protein (CRALBP), which we have shown to be an essential component of the visual cycle. [unreadable] [unreadable] During the proposed project period I will test the following hypotheses: (1) A PDZ-domain protein that interacts with CRALBP, is a scaffold protein for the assembly of a complex of CRALBP and other proteins in RPE and perhaps Muller apical microvilli. (2) Release of 11-cis-retinal from CRALBP occurs during its oxidation from 11-cis-retinol or may require modification of the binding protein. (3) CRALBP in Muller cells is involved in cone visual pigment regeneration. [unreadable] [unreadable] The new information will be applied towards an understanding and amelioration of inherited and acquired defects in human retinal. [unreadable] [unreadable]